Erectile Dysfunction (ED) is a kind of diseases characterized by the inability to develop an erection of the penis, the inability to get the erection stronger, or the inability to maintain an erection, which may lead to the failure of a sexual performance. There are many causes of Erectile Dysfunction. The first cause which can lead to Erectile Dysfunction is a psychological cause such as the bad relationship between the couples, or the mental stress caused by some reasons. The second cause is a physiological cause such as the disorder of the erection center. The severe diseases, especially the long-term diseases of some important organs such as liver, kidney, heart, lung may also influence the mental control of sexual physiology. The incidence rate of Erectile Dysfunction will increase along with the increase of age. According to the survey in normal population in USA, the incidence rate was 8% in adult men, whereas the incidence rate was approximately 10% in China.
Nowadays, there are many kinds of methods for treating Erectile Dysfunction, among which the oral administration of drugs is most acceptable. Commercial drugs for oral administration for treating Erectile Dysfunction are mainly Sildenafil (Trade name: Viagra), Tadalafil (Trade name: Cialis), Vaedenafil (Trade name: Levitra).
Sildenafil, Tadalafil and Vaedenafil are all selective inhibitors of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase-5 (PDE5). The physiological mechanism of an erection of penis relates to the release of nitric oxide (NO) in the corpus cavernosum of penis during a sexual stimulus. NO activate guanylate cyclase, and then leads to the enhancement of cyclic guanosine monophosphate (cGMP) level, the relaxation of the smooth muscles in corpus cavernosum, and the sufficiency of blood. The tissue concentration of cGMP can be regulated with phosphodiesterase, and the most abundant phosphodiesterase in corpus cavernosum is the cGMP-specific phosphodiesterase-5 (PDE-5). Drugs such as Sildenafil enhance the effect of nitric oxide by inhibiting phosphodiesterase type 5 (PDE5), which decompose cGMP in corpus cavernosum. When a local NO release has been raised by a sexual stimulus, drugs such as Sildenafil can inhibit PDE-5, enhance cGMP level in corpus cavernosum, relax the smooth muscles, force blood to flow into corpus cavernosum, and then initiate an erection.
It has been proved by clinical researches in many countries around the world that Sildenafil is effective to Erectile Dysfunction caused by many kinds of reasons, and thus is a safe, effective, convenient drug for treating ED. However, drugs such as Sildenafil have some clinical side effects such as headache, rubeosis, dyspepsia, nasal obstruction and paropsia, and may even cause cardiovascular diseases such as the decline of supine blood pressure and the decline of cardiac output. Moreover, it is indicated by clinical researches that when a sexual performance is carried out after the administration of Sildenafil, the incidence rate of a cardiac disorder including symptoms such as angina pectoris, dizziness, nausea, etc. will increase, and may lead to cardiogenic sudden death.
Nowadays, as reported in EP0463756, CN1358722A, CN1283624A, etc., there are many methods for synthesizing Sildenafil in the world, which can be divided into two types:
(1) Firstly, an intermediate 1-methyl-2-phenyl-3-n-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidine-7-one is synthesized, then a sulfonyl chloride group is introduced into the benzene ring by the reaction with chlorosulfuric acid, and finally, it is linked with N-methylpiperazine and form a salt with citric acid.

(2) An reaction between 1-methyl-3-propyl-4-aminopyrazole-5-carboxamide and 2-ethoxy-5-(4-methylpiperazine-1-sulfonyl)-benzoyl chloride is performed, and then Sildenafil is obtained by ring closure.

Further, we have found that when using a new compound obtained by using N-methylhomopiperazine instead of N-methylpiperazine during the synthesis of Sildenafil to perform animal experiments, the effective drug duration of the new compound is highly improved in comparison with Sildenafil under the same administration dosage during the treatment of Erectile Dysfunction, and the onset time thereof becomes short, and the toxicity and side effects thereof is declined.
Therefore, the present invention will disclose a 2-phenylpyrazolopyrimidone derivative for treating male Erectile Dysfunction.